ABSTRACT - Overall The overall significance of this program is that it will contribute to fulfilling the national need for specific pathogen free (SPF), Indian-origin, rhesus monkeys (Macaca mulatta) for AIDS-related research. SPF status will be ensured using state of the art viral testing methods, while genetic management will provide animals of known genetic relationships derived from two genetically diverse colonies. Animals will be characterized for both MHC Class I alleles and more than 50,000 SNPs by genomic sequencing. The Southwest National Primate Research Center (SNPRC) is in a unique position to provide genetically characterized animals, since it houses two large, genetically distinct colonies that will be selectively cross bred for genetic diversity. Colony 1 represents the original SNPRC colony supported and expanded through the previous efforts of this program (under SNPRC management since 2000), while Colony 2 is a new colony to this program initiated in 2015 with 237 animals derived from a distinct well-characterized SPF colony (SPF colony initiated in 1988). The specific aims are as follows: 1. To make approximately 110 pedigreed SPF, Indian-origin, rhesus macaques available for research annually. The colony is at a steady-state census and will be maintained at approximately 758 animals with 49 breeding groups. We will maximize the long term efficiency of colony production by genetically and reproductively managing the colony. 2. To verify and maintain the SPF4 status of the colonies by screening for herpes B virus, SIV, SRV, and STLV-1. All animals in the colony are screened two times per year for serology using the Luminex technology with beads containing two antigens for each virus. Confirmatory screening by western blot and PCR will be outsourced to California NPRC and the National B virus laboratory. 3. To maximize the value of the animals for AIDS-related research purposes by characterizing them for MHC Class I and Class II alleles. All new progeny will be typed for MHC haplotypes using deep sequencing at the Wisconsin NPRC. The MHC Class I data will be used to maintain diversity in haplotypes, while ensuring appropriate frequencies of specific alleles for AIDS research. High throughput genomic sequencing will provide the genetic markers to ensure Indian-origin and pedigree, but will also increase the capacity for genetic management of the colony and the ability to provide animals with greater genetic characterization to investigators. Fulfillment of these aims will contribute to ensuring that the supply of Indian-origin, SPF, rhesus monkeys is sufficient to meet the needs of the national AIDS research programs.